ABSTRACT
Lipid droplets (LDs) form inter-organelle contacts with the endoplasmic reticulum (ER) that promote their biogenesis, while LD contacts with mitochondria enhance ß-oxidation of contained fatty acids. Viruses have been shown to take advantage of lipid droplets to promote viral production, but it remains unclear whether they also modulate the interactions between LDs and other organelles. Here, we showed that coronavirus ORF6 protein targets LDs and is localized to the mitochondria-LD and ER-LD contact sites, where it regulates LD biogenesis and lipolysis. At the molecular level, we find that ORF6 inserts into the LD lipid monolayer via its two amphipathic helices. ORF6 further interacts with ER membrane proteins BAP31 and USE1 to mediate ER-LDs contact formation. Additionally, ORF6 interacts with the SAM complex in the mitochondrial outer membrane to link mitochondria to LDs. In doing so, ORF6 promotes cellular lipolysis and LD biogenesis to reprogram host cell lipid flux and facilitate viral production.
Subject(s)
Coronavirus , Coronavirus/metabolism , Endoplasmic Reticulum/metabolism , Lipid Droplets/metabolism , Lipolysis , Fatty Acids/metabolismABSTRACT
Objectives: Sacral neuromodulation is an effective, minimally invasive treatment for refractory lower urinary tract dysfunction. However, regular postoperative programming is crucial for the maintenance of the curative effects of electronic sacral stimulator devices. The outbreak of coronavirus disease 2019 (COVID-19) limited the ability of practitioners to perform traditional face-to-face programming of these stimulators. Therefore, this study aimed to evaluate the application of remote programming technology for sacral neuromodulation during the COVID-19 pandemic in China. Materials and methods: We retrospectively collected data including baseline and programming information of all patients with lower urinary tract dysfunction who underwent sacral neuromodulation remote programming in China after the outbreak of COVID-19 (i.e., December 2019). The patients also completed a self-designed telephone questionnaire on the subject. Results: A total of 51 patients from 16 centers were included. They underwent 180 total remote programming visits, and 118, 2, 25, and 54 voltage, current, pulse width, and frequency adjustments, respectively, were performed. Additionally, remote switching on and off was performed 8 times; impedance test, 54 times; and stimulation contact replacement, 25 times. The demand for remote programming was the highest during the first 6 months of sacral neuromodulation (average, 2.39 times per person). In total, 36 out of the 51 patients completed the questionnaire survey. Of these, all indicated that they chose remote programming to minimize unnecessary travel because they had been affected by COVID-19. The questionnaire also showed that remote programming could reduce the number of patient visits to the hospital, save time, reduce financial costs, and would be easy for patients to master. All surveyed patients indicated that they were satisfied with remote programming and were willing to recommend it to other patients. Conclusion: Remote programming for sacral neuromodulation is feasible, effective, safe, and highly recommended by patients with refractory lower urinary tract dysfunction. Remote programming technology has great development and application potential in the post-pandemic era.
ABSTRACT
This essay provides a brief introduction of a social-worker-led interdisciplinary work model and its operating process which is inspired by the well-known Holistic Model of Spirituality. The Interdisciplinary Bridging Response Team(IBRTs) model was applied to communities, centralized isolation sites, and shelter hospitals in Wuhan. A survey of 316 clients after 53 days of service revealed that the mental and physical health of most clients improved. Moreover, compared to the early days of the pandemic, most clients' social relationships were strengthened. Nevertheless, the World Health Organization Quality of Life (WHOQOL)-BREF scores show that this service was more effective for uninfected rather than infected people. (PsycInfo Database Record (c) 2022 APA, all rights reserved) Abstract (French) Cet essai fournit une breve introduction d'un modele de travail interdisciplinaire dirige par un travailleur social et de son processus de fonctionnement qui s'inspire du celebre modele holistique de spiritualite. Le modele d'equipes interdisciplinaires d'intervention de transition (IBRT) a ete applique aux communautes, aux sites d'isolement centralises et aux hopitaux-abris a Wuhan. Un sondage aupres de 316 client.e.s apres 53 jours de service a revele que la sante mentale et physique de la plupart des client.e.s s'est amelioree. De plus, par rapport aux premiers jours de la pandemie, les relations sociales de la plupart des client.e.s se sont renforcees. Neanmoins, les scores WHOQOL-BREF montrent que ce service etait plus efficace pour les personnes non infectees que pour les personnes infectees. (PsycInfo Database Record (c) 2022 APA, all rights reserved) Abstract (Spanish) Este ensayo proporciona una breve introduccion de un modelo de trabajo interdisciplinario dirigido por trabajadores sociales y su proceso operativo, inspirado en el conocido Modelo Holistico de Espiritualidad. El modelo de equipos de respuesta puente interdisciplinarios (EIRP) se aplico a comunidades, sitios de aislamiento centralizados y hospitales refugio en Wuhan. Una encuesta de 316 clientes despues de 53 dias de servicio revelo que la salud fisica y mental de la mayoria de los clientes mejoro. Ademas, en comparacion con los primeros dias de la pandemia, se fortalecieron las relaciones sociales de la mayoria de los clientes. No obstante, las puntuaciones del WHOQOL- BREF muestran que este servicio fue mas eficaz para las personas no infectadas que para las infectadas. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
ABSTRACT
ER-phagy is a form of autophagy, which is mediated by ER-phagy receptors and selectively degrades endoplasmic reticulum (ER). RNA viruses have been shown to utilize the ER as a membrane source to establish their replication organelles double-membrane vesicles (DMVs). However, whether viruses modulate ER-phagy to drive viral DMV formation and its underlying molecular mechanisms remain largely unknown. Here, we demonstrate that coronavirus subverts ER-phagy by hijacking the ER-phagy receptors FAM134B and ATL3 into p62 condensates, resulting in increased viral replication. Mechanistically, we show that viral protein ORF8 binds to and undergoes condensation with p62. FAM134B and ATL3 interact with homodimer of ORF8 and are aggregated into ORF8/p62 liquid droplets, leading to ER-phagy inhibition. ORF8/p62 condensates disrupt ER-phagy to facilitate viral DMV formation and activates ER stress. Together, our data highlight how coronavirus modulates ER-phagy to drive viral replication by hijacking ER-phagy receptors. Graphical abstract Tan et al. describe an important mechanism by which SARS-CoV-2 protein ORF8 inhibits ER-phagy by hijacking the receptors FAM134B and ATL3 into p62 condensates, facilitating the production of viral replication organelle double membrane vesicles.
ABSTRACT
ER-phagy is a form of autophagy that is mediated by ER-phagy receptors and selectively degrades endoplasmic reticulum (ER). Coronaviruses have been shown to use the ER as a membrane source to establish their double-membrane vesicles (DMVs). However, whether viruses modulate ER-phagy to drive viral DMV formation and its underlying molecular mechanisms remains largely unknown. Here, we demonstrate that coronavirus subverts ER-phagy by hijacking the ER-phagy receptors FAM134B and ATL3 into p62 condensates, resulting in increased viral replication. Mechanistically, we show that viral protein ORF8 binds to and undergoes condensation with p62. FAM134B and ATL3 interact with homodimer of ORF8 and are aggregated into ORF8/p62 liquid droplets, leading to ER-phagy inhibition. ORF8/p62 condensates disrupt ER-phagy to facilitate viral DMV formation and activate ER stress. Together, our data highlight how coronavirus modulates ER-phagy to drive viral replication by hijacking ER-phagy receptors.
ABSTRACT
As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains a membrane protein (M) that mediates viral release from cellular membranes. However, the molecular mechanisms of SARS-CoV-2 virion release remain poorly understood. In the present study, we performed RNA interference (RNAi) screening and identified the E3 ligase RNF5, which mediates the ubiquitination of SARS-CoV-2 M at residue K15 to enhance the interaction of the viral envelope protein (E) with M, whereas the deubiquitinating enzyme POH1 negatively regulates this process. The M-E complex ensures the uniform size of viral particles for viral maturation and mediates virion release. Moreover, M traffics from the Golgi apparatus to autophagosomes and uses autophagosomes for virion release, and this process is dependent on RNF5-mediated ubiquitin modification and M-E interaction. These results demonstrate that ubiquitin modification of SARS-CoV-2 M stabilizes the M-E complex and uses autophagosomes for virion release. IMPORTANCE Enveloped virus particles are released from the membranes of host cells, and viral membrane proteins (M) are critical for this process. A better understanding of the molecular mechanisms of SARS-CoV-2 assembly and budding is critical for the development of antiviral therapies. Envelope protein (E) and M of SARS-CoV-2 form complexes to mediate viral assembly and budding. RNF5 was identified to play a role as the E3 ligase, and POH1 was demonstrated to function as the deubiquitinating enzyme of SARS-CoV-2 M. The two components collectively regulate the interaction of M with E to promote viral assembly and budding. Ubiquitinated M uses autophagosomes for viral release. Our findings provide insights into the mechanisms of SARS-CoV-2 assembly and budding, demonstrating the importance of ubiquitination modification and autophagy in viral replication.
ABSTRACT
This essay provides a brief introduction of a social-worker-led interdisciplinary work model and its operating process which is inspired by the well-known Holistic Model of Spirituality. The Interdisciplinary Bridging Response Team(IBRTs) model was applied to communities, centralized isolation sites, and shelter hospitals in Wuhan. A survey of 316 clients after 53 days of service revealed that the mental and physical health of most clients improved. Moreover, compared to the early days of the pandemic, most clients’ social relationships were strengthened. Nevertheless, the World Health Organization Quality of Life (WHOQOL)-BREF scores show that this service was more effective for uninfected rather than infected people. [ABSTRACT FROM AUTHOR] Copyright of International Social Work is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
PURPOSE: The aim of this study was to examine the behavioral responses of pregnant women during the early stage of Coronavirus Disease 2019 (COVID-19) outbreak. METHODS: We recruited 1,099 women to complete an online questionnaire survey from February 10 to February 25, 2020. The subjects were divided into two groups (the pregnant women group and the control group). RESULTS: Concerns about infection: most of the participants watched the COVID-19 news at least once a day. Protective behaviors: the utilization rate of pregnant women (often using various measures) was higher than that of nonpregnant women. Exercise: 30.6% of the pregnant women continued to exercise at home, whereas in the control group, this percentage was 8.4%. Spouse relationship: 38.8% of the subjects' relationship improved, whereas only 2.3% thought the relationship was getting worse. CONCLUSION: Pregnant women had some unique behavioral responses different from that of nonpregnant women. It is important to understand the behavioral responses of pregnant women in this network era.
Subject(s)
Anxiety/epidemiology , Anxiety/psychology , COVID-19/psychology , Depression/psychology , Pregnancy Complications, Infectious/psychology , Pregnant Women/psychology , Adult , COVID-19/epidemiology , China , Cross-Sectional Studies , Depression/epidemiology , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/prevention & controlABSTRACT
OBJECTIVE: Mental health professionals are often exposed to workplace violence (WPV) in China. This study examined the prevalence of WPV and the associated factors and quality of life (QOL) among frontline mental health professionals during the COVID-19 pandemic. METHODS: This national survey was carried out between March 15 and March 20, 2020. WPV and QOL were assessed with standardized measures. RESULTS: A total of 10,516 participants were included. The prevalence of overall WPV was 18.5% (95% CI: 17.9%-19.3%), while verbal abuse/threats was 15.8% and physical violence was 8.4%. Multiple logistic regression analysis revealed that male gender (OR = 1.42, p < 0.01), higher educational level (OR = 1.40, p < 0.01), working in tertiary hospitals (OR = 1.33, p < 0.01), caring for COVID-19 patients (OR = 3.10, p < 0.01) and having more severe anxiety symptom (OR = 1.21, p < 0.01) were positively associated with WPV. In contrast, working in inpatient departments (OR = 0.74, p < 0.01), having longer work experience (OR = 0.99, p = 0.03), and being a junior nurse (OR = 0.73, p < 0.01) were negatively associated with WPV. After controlling for the covariates, mental health professionals who experienced WPV had a lower overall QOL compared to those without WPV (F(1, 10515) = 68.28, p < 0.01). CONCLUSION: This study found that WPV was common among mental health professionals in China during the COVID-19 pandemic. Considering the negative impact of WPV on QOL and quality of patient care, appropriate measures to prevent WPV should be developed.